1. Technical Field of the Invention
The present invention relates to novel 7-oxo-DHEA derivatives, to a process for synthesizing such novel compounds and to cosmetic/therapeutic compositions comprising same.
The present invention also relates to cosmetic applications of at least one 7-oxo-DHEA derivative to improve the appearance of keratin materials and substrates, such as the skin, the hair, the eyelashes and the nails, in particular to prevent or treat adverse signs of aging of the skin and/or a dull complexion and/or skin or hair pigmentation disorders and/or dryness of the skin and/or hyperseborrhoea and/or hyperseborrhoea-related imperfections and/or sensitive skin and/or dandruff and/or natural hair loss and/or baldness.
This invention also relates to a cosmetic regime/regimen for treating keratinous substrates/materials by topical application thereon of a composition containing at least one 7-oxo-DHEA derivative, formulated into a physiologically acceptable medium therefor.
2. Description of the Prior Art
DHEA, or dehydroepiandrosterone, is a natural steroid produced essentially by the adrenal glands. Exogenous DHEA, administered topically or orally, is recognized for its capacity to promote epidermal keratinization (JP-07,196,467) and to treat dry skin by increasing the endogenous production and secretion of sebum and thus by reinforcing the skin's barrier effect (U.S. Pat. No. 4,496,556). U.S. Pat. No. 5,843,932 has also described the administration of DHEA to remedy dermal atrophy by inhibiting the loss of collagen and of connective tissue. Too, the assignee hereof has demonstrated the capacity of DHEA to combat the weathered appearance of the skin (FR-00/00349), to modify skin and hair pigmentation (FR-99/12773) and to combat epidermal atrophy (FR-00/06154). These properties of DHEA make it a candidate of choice as an anti-aging active agent.
However, DHEA has hormonal effects that may prove difficult as regards the administration of same. There need still exists to provide DHEA analogs with properties as advantageous as DHEA itself, but without eliciting any hormonal effects.
It was first considered by applicants that the 7-oxo-DHEA derivatives of general formula (I) below could satisfy this need: 
Among these compounds, 3β-acetoxy-7-oxo-DHEA or Δ5-androstene-3β-acetoxy-7,17-dione is already known and has been described as being effective in modulating the immune system (U.S. Pat. Nos. 5,292,730, 5,585,371 and 5,641,766), treating Alzheimer's disease (U.S. Pat. No. 5,707,983), treating HIV syndrome (U.S. Pat. No. 5,885,977) and for promoting weight loss (U.S. Pat. Nos. 5,296,481 and 5,807,848).
WO-99/25333 also indicates the administration, especially topically, of 3β-acetoxy-7-oxo-DHEA in the prophylactic and curative treatment of lupus erythematosus, which is a disorder of the immune system that is liable to affect several organs and that is manifested in the skin by transverse redness of the face and/or by squamous erythemal plaques disseminated over the body.
U.S. Pat. No. 5,424,463 especially describes 7-keto-DHEA (or Δ5-androstene-3β-ol-7,17-dione) and derivatives thereof wherein one or more of the hydroxyl or keto substituents is a group convertible thereto by hydrolysis. Hydrolyzable groups include hydroxyl groups esterified with an acid selected from the group consisting of (i) a normal, branched, saturated or unsaturated C2-C22 aliphatic acid, (ii) a C7-C22 aromatic acid, (iii) a C3 or more dicarboxylic acid, for which only one carbonyl group is esterified with the 3-hydroxy group of the steroid, (iv) an inorganic acid such as sulfuric acid and phosphoric acid. U.S. Pat. No. 5,424,463 describes the 7-keto- and hydrolyzable derivatives thereof as being effective for promoting weight loss.
In addition, the following derivatives are also described as being effective for promoting weight loss (Steroids, 1998, 63(3), pp. 158-165): 3β-O-acetyl-7-oxo-dehydroepiandrosterone (or 3β-acetyl-7-oxo-DHEA);                3β-O-propionyl-7-oxo-dehydroepiandrosterone (or 3β-propionyl-7-oxo-DHEA);        3β-O-butanoyl-7-oxo-dehydroepiandrosterone (or 3β-butanoyl-7-oxo-DHEA);        3β-O-isobutanoyl-7-oxo-dehydroepiandrosterone;        3β-O-heptanoyl-7-oxo-dehydroepiandrosterone;        3β-O-dodecanoyl-7-oxo-dehydroepiandrosterone;        3β-O-palmitoyl-7-oxo-dehydroepiandrosterone;        3β-O-stearoyl-7-oxo-dehydroepiandrosterone;        3β-O-hemisuccinate-7-oxo-dehydroepiandrosterone.        
Among the 7-oxo-DHEA derivatives of formula (I) that are described in the prior art are the following derivatives:                (1) The derivative of formula (I) in which R is a 2-tetrahydropyran group (RN 102 890-86-8).        (2) The compound of formula (I) in which R is a CH3OCO group, described as suppressing the transactivation of the androgenic receptor induced by an androstenediol in human prostate cancer cells (Proc. Natl. Acad. Sci. USA, 1999, 96(20), pp. 11173-11177).        (3) Derivatives of formula (I) in which R is an O═P(OH)OCOCH3 group or a group described in U.S. Pat. No. 5,837,269 as agents for increasing the immune response to a vaccine.        (4) The derivative of formula (I) in which R is a group mClPhCO, described in an epoxidation process for the synthesis of steroids (J. Chem. Soc. Perkin Trans. I, 1975 (4), pp. 323-6).        (5) Derivatives of formula (I) in which R is an NaSO3H group or an SO3H group, noted in Endocrinol. Exp., 1971, 5(4), pp. 205-210, which describes the properties of these derivatives when they are subjected to various hydrolysis conditions.        (6) The derivative of formula (I) in which R is a tBuSi(Me)2 group, described in a steroid preparation process (Heterocycles, 1994, 38(5), pp. 1053-60).        
However, to the knowledge of applicants, it was heretofore unknown to administer the 7-oxo-DHEA derivatives of general formula (I) for cosmetic purposes, in particular for treating the adverse signs of aging.